Each day children and adolescents^† face a wide range of medical illnesses including allergies, asthma, epilepsy, cancer, diabetes, and obesity, all of which appear to be increasing in prevalence.¹ According to the 2005 to 2006 National Survey of Children with Special Health Care Needs Chartbook, the two most common are allergies (53%) and asthma (38.8%).² The increasing prevalence of these has been partly attributed to medical advances that have reduced mortality rates, so that children with chronic medical conditions now live longer.^3,4 The increased prevalence of childhood illnesses is also related to increased exposure to toxic stress, sedentary lifestyle, and an unhealthy diet leading to increased childhood obesity and subsequently other comorbid medical disorders.³

Ten to twenty million children in the United States have a medical condition, and about 10% of them are impacted by it in their daily lives.⁵ Illnesses affect the emotional and social wellbeing of children and their parents, and increase the stress-level of the family system as well.⁶ For example, illness characteristics (such as pain or fatigue) and required treatments (such as steroid medication) can interfere with school participation, which in turn can lead to academic difficulties and social isolation as well as increased caregiving and financial demands on their parents. Children with chronic illness are also more prone to bullying by peers,⁷ which can then further exacerbate their physical symptoms and lead to greater psychological distress.⁸ While the majority of children with medical illness are resilient,⁵ when compared to their healthy counterparts, they have an increased risk for the development of psychiatric problems.^6,9,10 It is estimated that 20% of children with chronic health conditions will have psychiatric problems.⁵

Children with medical illness can present with both internalizing and externalizing psychiatric problems. Internalizing problems are manifested in symptoms of depression, anxiety and somatic complaints whereas externalizing problems are reflected in hyperactivity, aggression, or “acting-out” (Table 20-1). That said, internalizing problems tend to occur more frequently in medically ill children.^11,12 For example, a meta-analysis assessing behavioral outcomes of children with medical illness concluded that internalizing symptoms were more prominent than externalizing symptoms.¹³ It is hypothesized that certain characteristics associated with physical illness, such as the sense of losing control, restrictions of positive activities, isolation from peers, and pain, are the driving force for the development of internalizing symptoms.

This chapter focuses specifically on diagnostic considerations and challenges in psychiatric assessment and differential diagnosis of depression in children with medical illness. Asthma, obesity, epilepsy, cancer, and diabetes mellitus are specifically reviewed. Treatment-related issues and the recommendations of the American Academy of Child and Adolescent Psychiatry are considered.

Children with medical illness are more prone to develop depressive disorders.^14,15 The overall prevalence of depressive disorders in the general population is approximately 2% in children and 6% in adolescents,¹⁶ with another estimated 5% to 10% having subsyndromal symptoms of depression.¹⁷ Children with physical illness are approximately twice as likely to develop depression as their healthy counterparts,¹⁸ and because they often present with subsyndromal symptoms they are not always accurately diagnosed.¹⁹

Though the evidence suggests that acute medical illness increases the risk of developing depression in childhood, the long-term effects of childhood medical illness on adult psychological adjustment are less clear. One important study found no difference in prevalence of psychiatric disorders among young adults who had experienced childhood medical illness and those who had not;²⁰ however, the severity of psychiatric symptoms in the adults was greater in those who had experienced more severe illnesses in childhood. A comprehensive literature review reported that the overall prevalence of psychiatric disorders in young adult survivors of childhood medical illness was similar to that of their healthy counterparts, but that social adjustment was significantly more impaired in those who had experienced chronic childhood illnesses.¹⁹ It also appears that subsyndromal symptoms of depression in medically ill children and adolescents may have an effect on social and functional outcomes in adulthood.¹⁹ This underscores the need for early detection and treatment of psychiatric comorbidity in these children.

Depression in children presents with a similar picture to that in adults. According to the Diagnostic and Statistical Manual, 5th Edition (DSM-5)²¹ children can be diagnosed with major depressive disorder (MDD) if they have persistent depressed or irritable mood for at least 2 weeks accompanied by loss of pleasure and interest in activities, changes in sleep and appetite and feelings of worthlessness and suicidal ideation. While the DSM-5 criteria for MDD are similar for adults and children, there are some important differences when it comes to clinical presentation, which are attributed to the developmental stage of the child.

Children tend to present with fewer melancholic symptoms and are less likely to verbalize feelings of depression. Instead they may present with temper tantrums, irritability, social isolation, and somatic symptoms.¹⁷ The high rates of somatic symptoms present a challenge when trying to diagnose depression in a medically ill child because the symptoms of the illness can either be misperceived as depression, or a diagnosis of depression may be delayed because of attributing such symptoms directly to the medical illness.²² Children’s developmental stage, their understanding of their medical illness and their ability to express their feelings may present an additional challenge when evaluating the presence of a depressive disorder.

Similar to MDD, the diagnostic criteria for persistent depressive disorder are comparable in children and adults, with the exception of the duration of illness which is one year of persistent low or irritable mood along with changes in sleep, appetite, and energy levels instead of 2 years in adults.²¹

Depressive symptoms in medically ill children may range from a transient mood change requiring no treatment to a severe clinical disorder requiring psychiatric hospitalization.¹⁸ Thus, mental health classification systems, with their focus on diagnosable disorder may be of little value to primary care physicians who deal with the whole spectrum of mental health symptoms.¹⁸ In order to address the wide range of symptoms, the American Academy of Pediatrics introduced The Classification of Child and Adolescent Mental Diagnoses in Primary Care, Child and Adolescent Version which provides a system to classify symptoms ranging from developmental variation to problem to disorder.²³

Underdiagnosis of depression in the face of medical illness²⁴ is a missed opportunity to improve quality of life, increase adherence to treatment and shorten hospital stays, all of which are themselves associated with improvement in depressive symptoms.¹⁸ There are many different reasons for underdiagnosis and misdiagnosis of depression in children with illnesses. For example, irritable mood and somatic symptoms may be more prominent than depressed mood. Parents and children are more likely to focus on somatic complaints than mood or cognitive symptoms. Primary care clinicians may be reluctant to raise concerns of psychiatric symptoms to avoid stigmatizing patients.²⁵ These facts further highlight the importance of early screening and accurate assessment of depression in children who are ill.

Diagnosing depression in children is not infrequently complicated by the presence of co-occurring anxiety. Box 20-1 presents some of the psychological factors that may contribute to clinically significant anxiety in medically ill children (Box 20-1).

The assessment of depression in children who are ill begins with a psychiatric examination for psychological and somatic symptoms consistent with the DSM-5 criteria for a depressive episode. The examination should lead to accurate diagnosis along with a developmentally informed biopsychosocial formulation²⁶ whereby the child’s presentation should be seen in light of a continuum of depressive symptoms.²³ In the examination, the following factors are important to consider when developing an accurate biopsychosocial formulation for medically ill children.

CHILD-RELATED FACTORS

The level of psychological distress experienced will depend on certain personal characteristics. Low IQ and low self-esteem are two risk factors that can predispose medically ill children to develop depressive disorders.²⁶ The child’s coping style (i.e., maladaptive, catastrophizing) can also influence their psychological adjustment.²⁶

DEVELOPMENTAL FACTORS

While children’s approach to their illnesses will in part be shaped by their prior experiences with medical conditions,²⁷ developmental stage is a critical consideration as children’s understanding of their illness directly affects their cognition and emotions.²⁸ Very young children are limited in their cognitive understanding and ability to remember information about their condition, which may result in adverse behaviors around medical procedures.^29,30

Although various theories have been proposed to explain children’s understanding of illness,³¹ Piaget’s stages of cognitive development still offer a pragmatic approach to comprehending their view of medical illness (Fig. 20-1).^32,33 Young children who are in the pre-operational phase classically interpret their illness as a form of punishment and feel that they have caused the illness by doing something wrong or being bad. They may attribute illness to magic or evil³⁴ and assume that all illnesses are contagious. By school age, children develop concrete operations, and become aware of other factors (i.e., “germs”) that can cause illness. These older children are prone to feeling a loss of control, anxiety, and significant fear about harm to their bodies,²⁸ which can put them at higher risk for the development of depression.

Adolescents who are in the process of developing formal operations, have a more complex understanding of illness including the interactions of various organ systems.³⁵ Illness in this age group has the potential to significantly interfere with the adolescent developmental tasks of individuation, identity formation and sexuality, particularly in the presence of medical conditions that can cause loss of function or change in appearance.²⁸ A young child experiencing hair loss due to chemotherapy may be less affected than an adolescent in a similar situation. The interference with normal developmental tasks can heighten the risk for depression in adolescents.

FAMILY FACTORS

Childhood medical illness affects family dynamics, caregiver burden and parental vulnerability to stress.⁶ At the same time the family’s ability to manage a child’s illness in turn impacts the child’s ability to cope with his/her illnesses.^25,28 Thus, when assessing medically ill children, it is important to consider the developmental stage of the family.

The life cycle of the family, and the developmental tasks associated with each stage, have been described and characterized as families with young children, families with adolescents, and families with children who are young adults.³⁶ Families with young children have to focus on children’s development while building confidence in their parenting skills. In contrast families with adolescents have to embrace the adolescent’s gradual independence while continuing to maintain family boundaries and responsibilities. As adolescents transition into young adulthood families continue to promote the establishment of new relationships outside the family along with medical and financial independence. When childhood illness occurs at any of these phases it can impact the developmental tasks of the entire family. When a young child is ill, the family may have trouble setting appropriate limits, which can lead to “acting-out.” When adolescents are ill, they may not be able to work on achieving independence, which may lead to feelings of insecurity and depression as well as frustration for the family. Similarly, young adults who become ill may be prevented from achieving developmental milestones, such as higher level of education, or financial independence and career planning, which can add more burdens to the individual and the family system. Parental divorce, insufficient funds, and poor parental adjustment to the child’s condition have been associated with poor adjustment in children with medical illness.³⁵

SUICIDAL RISK

Unlike adult studies, pediatric studies have not found an association between suicidal thoughts and specific medical conditions (such as cancer).³⁷ However, studies in children have noted increased rates of suicidal behaviors when the chronic medical illness co-occurs with significant psychiatric disorder.^38,39 Medically ill children who attempt suicide have similar risk factors to physically healthy children.¹⁸ Exposure to childhood sexual abuse, unsupportive parental relationships, and limited parental involvement as well as mood disorders, substance abuse, and antisocial behaviors have all been linked with increased risk for suicide in children.⁴⁰ Family history and prior history of suicidality are additional risk factors, as is access to lethal means.

In the medical setting, it is important to consider the following three diagnostic categories in the differential diagnosis—primary depressive disorder, depressive disorder as a reaction to medical illness, and secondary depressive disorder due to a general medical condition. All three entities can be involved to some degree in any single patient and as a result can create a significant challenge in determining which is the primary diagnosis underlying the depressive symptoms.

PRIMARY DEPRESSIVE DISORDERS

Children with medical illness who meet DSM-5 criteria can be diagnosed with a co-occurring major depressive episode. While there is overlap in neurovegetative symptoms between the direct effects of a general medical condition and a depressive disorder, the preoccupation with worthlessness, hopelessness, inappropriate guilt, and suicidality are more consistent with a primary depressive disorder than either of the other two categories.¹⁸ The Children’s Depression Rating Scale Revised,⁴¹ which focuses on nonoverlapping symptoms and excludes somatic symptoms, has demonstrated high sensitivity for the clinical diagnosis of a primary depressive disorder in children with cancer.⁴² The Children’s Depression Inventory (CDI) accurately identified clinical depression in medically ill children and has been recommended for screening in the medical setting.²¹ The anhedonia subscale is the most highly correlated scale with a primary depressive disorder.²¹

As in the general population, prior episodes of depression and significant genetic loading through a family history of mood disorders are two major risk factors for the development of a primary depression in children with medical illness. Depression in the family of origin is the most important risk factor for the development of a depressive disorder.^42,43 Environmental factors such as abuse, neglect, loss, conflicts and stress, including that imposed by the presence of the medical illness, may contribute to the development of a primary mood disorder. There is an interaction effect between life stressors, subsyndromal depressive symptoms and a family history of depression that can lead to the development of a primary depressive disorder (Fig. 20-2).¹⁶